National In-Hospital Outcomes of Pregnancy in Women With Single Ventricle Congenital Heart Disease

Abstract

Most patients with single ventricle (SV) congenital heart disease are expected to survive to adulthood. Women with SV are often counseled against pregnancy; however, data on pregnancies in these women are lacking. We sought to evaluate in-hospital outcomes of pregnancy in women with SV. We used nationally representative data from the 1998 to 2012 National Inpatient Sample to identify women ≥18 years of age admitted to the hospital with International Classification of Diseases-9th Revision codes for an intrauterine pregnancy and a diagnosis of hypoplastic left heart syndrome, tricuspid atresia, or common ventricle. A matched comparison group without a diagnosis of congenital heart disease or pulmonary hypertension was identified from the database. National estimates of hospitalizations were calculated. Length of stay, hospital charges, and complications were analyzed and compared between groups. Charge data were adjusted to 2012 dollars. There were 282 admissions of pregnant women with SV (69% with deliveries) and 1,405 admissions in the control group (88% with deliveries). Vaginal delivery was more common in SV (74% vs 71%, p <0.001). Length of stay (4.1 ± 0.91 vs 2.8 ± 0.18 days, p <0.001) and charges ($30,787 ± 8,109 vs $15,536 ± 1,006, p <0.0001) were higher in the SV group. Complications occurred in most SV admissions and were more common in the SV group than in the control group. No deaths occurred. Cardiovascular complications occurred in 25% of pregnancy-related hospitalizations, although in-hospital pregnancy-related death is rare. Vaginal delivery is common in these patients. These data suggest that pregnancy and vaginal delivery can be tolerated in women with SV, although the risk for a cardiovascular event is significantly higher than in the general population.

Moderate or severe forms of congenital heart disease (CHD) occur in 6 in 1,000 live births,¹ and survival to adulthood is now expected in 90%.^2,3 Approximately 8% of all CHD is composed of defects palliated with a single ventricle (SV) strategy,¹ and among those, hypoplastic left heart syndrome (HLHS) is the most common. Advances in therapies have increased survival in HLHS from essentially zero to the current expectation that 70% of patients will survive to adulthood.⁴ As women with SV reach reproductive age, considerations of pregnancy and motherhood become increasingly important. Pregnancy risk for women with SV and a history of Fontan palliation is World Health Organization class III, indicating a significantly increased risk of maternal morbidity and mortality compared with the general population.⁵ As a result, these women have historically been advised against pregnancy.⁶ However, small studies have shown women with SV can tolerate pregnancy relatively well if their prepregnancy cardiovascular status is good,⁷ and the risk of maternal mortality in women with SV is low.⁸ These data are limited, and no studies have compared in-hospital, pregnancy-related events and mortality in women with SV with control women. The present study sought to characterize national trends of pregnancy-related hospital admissions for women with SV CHD, determine in-hospital pregnancy-related complications, and compare the hospitalizations of women with SV with contemporaneous controls.

Methods

Data were sourced from the 1998 to 2012 Healthcare Cost and Utilization Project National Inpatient Sample 2012 (NIS) (Agency for Healthcare Research and Quality, Rockville, Maryland, www.hcup-us.ahrq.gov/nisoverview. jsp). The NIS is the largest all-payor inpatient health care database in the United States, containing data from approximately 8 million hospital discharges per year, yielding a 20% stratified sample of all community hospitals. Earlier investigators have used the NIS to study trends in hospital resource utilization, including those trends involving adults with CHD.^9–11 We have used the NIS to examine risk factors for increased hospital resource utilization and mortality in adults with SV.¹² The institutional review board of the University of Arkansas for Medical Sciences waived the need for investigational approval because the secondary administrative data in the NIS are deidentified.

The data contained in the NIS database include detailed, deidentified information on each inpatient’s demographics, diagnoses, procedures, disposition on hospital discharge, and hospital charges. Data were limited to include only patients ≥18 years of age admitted to the hospital with a pregnancy-related diagnosis (Appendix) and with International Classification of Diseases-9th Revision (ICD-9) codes for a diagnosis of HLHS (ICD-9 746.7), tricuspid atresia (746.1), or common ventricle (745.3). Hospitalizations with molar or ectopic pregnancies were excluded. In addition, a 5:1 matched control group of women with a pregnancy-related diagnosis without the diagnosis of SV or pulmonary hypertension was created and used for comparisons. Matched variables included age, race, insurance type, and year of admission.

Collected data included patient demographics (age at admission, gender, race, ethnicity, and payor status), principal and secondary diagnosis codes, mechanical ventilation, procedures performed, duration of hospital length of stay (LOS) in days, in-hospital mortality, and hospital charges. All charge data were adjusted for inflation to 2012 dollars using Consumer Pricing Indices data. Co-morbid conditions most relevant to pregnant patients with SV were derived from principal and secondary ICD-9 diagnoses codes (Appendix).

Primary outcomes of interest were the total number of pregnancy-related inpatient admissions for women with SV; hospital resource utilization, measured by length of stay and charges per day; and the distribution of select co-morbid conditions.

The data use agreement of the NIS does not allow the presentation of any unweighted count <10. In situations when this is not the case, percentages for each group and the statistical test result are presented. In situations wherein the count is <10 for only one of the groups (SV vs control), the percentage of cases for the group >10 will be reported along with the statistical test result and a notation of the direction of the result.

All statistical analyses were carried out using SAS version 9.4 software (SAS Institute Inc., Cary, North Carolina). Because the NIS is complex survey data, we used SAS survey analysis procedures. Continuous and categorical outcomes were presented as means (standard error) and frequency (percentage), respectively. Comparisons of continuous outcomes between SV and controls, as well as SV anatomic subtypes and controls, were done using the analysis of variance test. Likewise, categorical outcomes were compared by use of the Rao-Scott chi-square test. Sampling weights were used in all analyses to produce nationally representative estimates while adjusting for clustering by hospital and the complex sampling design of the data. Statistical significance was determined at p values <0.05.

Results

There were a total of 282 intrauterine pregnancy-related hospital discharges of women with SV to US community hospitals during the 15-year study period. Demographic and admission-related distributions of SV and control hospitalizations are listed in Table 1. These data are reported by SV anatomic subtype in Table 2. The median number of annual hospital admissions was 15 (range 4 to 54) with no change in admission rate across the study period. No differences in SV pregnancy-related outcomes were found between teaching and nonteaching hospitals.

Table 1.

Baseline hospitalization data for pregnancy-related admissions of women with single ventricle congenital heart disease compared to matched controls

Variable	Single ventricle patients (N=282)	Controls (N=1405)	p-value
Age (years)	25.8±0.9	26.6±0.4	0.3637
Length of stay (days)	4.1±0.9	2.8±0.2	0.0303
Total hospital charges	$30,787±8,109	$15,536±1,006	0.0004
Teaching hospital	218 (77%)	662 (47%)	<0.0001
Admission type			0.0008
Antepartum	73 (26%)	144 (10%)
Delivery	194 (69%)	1241 (88%)
Postpartum	*	*
Delivery route			0.0006
Vaginal	144 (74%)	879 (71%)
Cesarean section	50 (26%)	362 (29%)
Delivery outcome			<0.0001
Liveborn	169 (87%)	1214 (98%)
Stillborn	*	*
Missing	*	*

Italicized values indicate a statistically significant results.

^*Indicates unweighted values > 0 but <10, which cannot be reported in accordance with data use agreement from the National Inpatient Sample.

Table 2.

Baseline hospitalization data for pregnancy-related admissions of women with single ventricle congenital heart disease by anatomic subtype

Variable	HLHS (N=36)	TA (N=201)	CV (N=45)	Controls (N=1405)	p-value
Age (years)	29.3±2.5	25.0±1.0	26.8±2.0	26.6±0.3	0.2154
Length of stay (days)	3.3±1.0	4.1±1.2	4.6±1.6	2.8±0.2	0.1559
Total hospital charges	$11,809±2,711	$26,263±8,879	$66,146±28,526	$15,536±996	<0.0001
Teaching hospital	31 (81.6%)	148 (73.6%)	40 (88.9%)	662 (47.1%)	0.0006
Admission type					N/A
Antepartum	6 (16.7%)	68 (33.8%)	-	144 (10.2%)
Delivery	30 (83.3%)	124 (61.7%)	40 (88.9%)	1241 (88.3%)
Postpartum	-	10 (5%)	5 (11.1%)	21 (1.5%)
Delivery route					0.9186
Vaginal	25 (83.3%)	90 (72.6%)	30 (75%)	879 (72.4%)
Cesarean section	5 (16.7%)	34 (24.4%)	10 (25%)	362 (27.6%)
Delivery outcome
Liveborn	*	108 (87.1%)	*	1214 (97.8%)
Stillborn	*	*	*	*
Missing	*	*	*	*

Italicized values indicate a statistically significant results.

^*Indicates unweighted values > 0 but <10, which cannot be reported in accordance with data use agreement from the National Inpatient Sample.

As listed in Table 3, cardiovascular complications occurred more commonly in hospitalizations of patients with SV (70 of 282 admissions, 24.8%) than in controls (<1%; p <0.0001). Arrhythmias were the most common cardiovascular complication in SV hospitalizations, occurring much more commonly (17.7% of admissions) than in controls (p <0.0001). The most common arrhythmia was atrial flutter, followed by atrial fibrillation, ventricular fibrillation, and paroxysmal atrial tachycardia. Heart failure occurred in <5% of SV admissions and was not reported in the control group. Similarly, cerebrovascular accidents occurred in <2% of SV hospitalizations, whereas none were reported in the control group. No deaths occurred in either the SV group or the control group. No cardiovascular complications occurred in isolation from obstetric complications in either group.

Table 3.

Cardiovascular and obstetric events among women with and without single ventricle cardiac defects admitted to a US hospital with a pregnancy diagnosis, 1998 – 2012

Event	Single ventricle patients (n = 282)		Controls (n = 1405)		p-value
	N	%	N	%
In-hospital mortality	-	-	-	-	-
Composite cardiovascular outcome*	70	24.8	†		<0.0001
Cardiovascular events
Myocardial infarction/ischemia	-	-	-	-	-
Cardiac arrest/ventricular fibrillation	†		-	-	-
Arrhythmia‡	50	17.7	†		<0.0001
Heart failure	†		-	-	-
Pulmonary events
Pneumonia	† §		†		0.0213
Pulmonary edema	-	-	†		-
Acute respiratory distress syndrome	†		-	-	-
Thromboembolic events
Pulmonary embolism	-	-	†		-
Deep vein thrombosis	-	-	-	-	-
Stroke-cerebrovascular accident	†		-	-	-
Infections
Sepsis	-	-	-	-	-
Renal event
Acute renal failure	†		†		0.2160
Composite obstetric events¶	146	51.8	347	24.7	<0.0001
Obstetric events
Gestational diabetes	† §		54	3.8	0.0185
Hypertensive disorders in pregnancy	†		108	7.7	0.5649
Preterm labor	51	18.1	120	8.5	0.0230
Placental abruption	†		†		0.6820
Fetal growth restriction	† §		†		<0.0001
Stillbirth/Intrauterine fetal death	†		†		0.0983
Placenta previa	-	-	-	-	-
Postpartum Hemorrhage	†		†		0.6728
Chorioamnionitis	†		†		0.6925

Italicized values indicate a statistically significant results.

^-Indicates no reported events.

^*Composite cardiovascular outcome includes myocardial infarction, cardiac arrest, arrhythmias, heart failure or stroke-cerebrovascular accident.

^†Indicates unweighted values > 0 but <10, which cannot be reported in accordance with data use agreement from the National Inpatient Sample.

^‡Indicates composite of atrial flutter, atrial fibrillation, and paroxysmal atrial tachycardia.

^§Indicates rate in single ventricle patients significantly higher than control rate.

^¶Composite obstetric events includes gestational diabetes, preeclampsia, eclampsia, gestational hypertension, preterm labor, placental abruption, fetal growth restriction, intrauterine fetal death, placenta previa, postpartum hemorrhage, or chorioamnionitis.

Obstetric complications without a concomitant cardiovascular complication occurred more frequently in controls than in patients with SV (51.8% vs 24.7%; p <0.0001). Patients with SV had higher rates of gestational diabetes, preterm labor and/or delivery, and fetal growth restriction. The odds ratio of preterm labor and delivery was 2.3 (95% confidence interval 1.04 to 5.15) in patients with SV compared with controls.

Discussion

Patients with SV CHD are now surviving to adulthood.⁴ Before the advent of the Fontan procedure for tricuspid atresia¹³ and the subsequent Norwood procedure for HLHS,¹⁴ survival beyond early infancy was rare. Now as women with SV survive to adulthood, the possibility of pregnancy becomes a significant consideration for many of them. The present study reports the largest ever cohort of pregnant women with SV and their in-hospital, pregnancy-related outcomes.

Complications occurred in nearly all pregnancy-related hospitalizations of women with SV, whereas complications occurred less commonly in controls. Cardiovascular complications occurred in nearly 1/4 of all admissions for women with SV. In a cohort of 25 patients with SV, Drenthen et al¹⁵ reported arrhythmias occurred in 16% and heart failure occurred in 4%. These data are comparable with those of the present study wherein arrhythmias occurred in 1/6 of admissions and heart failure occurred in <5%. Gouton et al¹⁶ reported only 6 qualifying cardiac complications in their study of 38 completed pregnancies in 37 women with SV. In that study, similar to the present study, atrial arrhythmias were the most common complication. All cardiovascular complications in the present study occurred in women who also had obstetric complications. The present data do not allow the determination of causality; however, this finding does raise the question as to whether the hemodynamic effects of obstetric complications played an integral role in the cardiovascular complications. This finding supports management strategies aimed at mitigating obstetric complications in women with SV.

Preterm delivery occurred in about 1/5 of SV hospitalizations resulting in a delivery. This rate is lower than that of previous reports. In smaller cohorts, previous authors have reported preterm delivery occurs in 28% to 69% of women who have undergone Fontan palliation.^15,16 The difference between the present study and these previous reports may be related to cases of spontaneous abortion, which occur in 30% to 50% of cases.^15–17 It is plausible that spontaneous abortions may have occurred in some cases and those women did not present to the hospital to be captured in the NIS database, thereby lowering what could have been a higher preterm birth rate. Conversely, the present study may be more accurate given the size of the cohort.

There were no maternal deaths in the study cohort. Although older recommendations were against pregnancy in women with SV,⁶ the present data demonstrated no in-hospital mortality in such patients. In addition, the mean length of stay in the SV group was only 1.3 days longer than in the control group, suggesting cardiovascular complications did not play a major role in the hospital course. Nevertheless, the composite cardiovascular complication of arrhythmias, cardiac arrest, heart failure, and stroke occurred in 1/4 of admissions. This level of risk is comparable with a cardiac disease in pregnancy (CARPREG) score of 1, indicating a significantly increased risk.¹⁸ Based on the present data, it seems reasonable that women with SV should be counseled that this is their baseline level of risk of a cardiovascular event during pregnancy.

Vaginal delivery occurred in 3/4 of deliveries. Earlier investigators have suggested that if the patient’s cardiovascular status is good, a trial of labor and vaginal delivery can be considered unless there are specific fetal or maternal indications to necessitate cesarean delivery.¹⁹ Similarly, Elkayam et al²⁰ recommended vaginal delivery for women with SV after Fontan operation in a review on the topic of high-risk cardiac disease in pregnancy. The results in this relatively large cohort support the recommendation for vaginal delivery in these patients.

The study is susceptible to the limitations of the NIS database, including the reliability of classifications and the ICD-9 codification.²¹ Other authors have successfully used the NIS¹⁰ and other ICD-9 code-driven administrative databases to study hospital resource utilization in adults with CHD.⁹ Although it is highly likely that the large majority of patients in the present study had previously undergone a Fontan operation, the nature of the database does not allow a determination to be made, and therefore, some of these patients may not have previously undergone a Fontan operation. Previous authors have used the ICD-9-Clinical Modification code 35.94 to identify patients who have previously undergone Fontan operations. However, this code represents a procedural code that should be used only during the specific hospitalization when the surgery occurred and therefore cannot, or should not, be considered to be a code to be used in patients with a history of previous Fontan surgery. The nature of the database does not allow the determination of initial surgical intervention versus revisions. The study was conducted using data from inpatient hospitalizations. Thus, the results of the study may not be applicable to all women with SV, especially those in the outpatient setting. Mortality data in the NIS are dependent on the accuracy and completeness of the administrative coding surrounding the individual admissions. In addition, outpatient mortality cannot be assessed using this inpatient database, and therefore, the mortality rates may be underestimated. The NIS does not allow tracking patients across multiple admissions. Medication administration data are not available in the NIS.